1. Field of the Invention
This invention relates to methods for coating drug delivery devices.
2. Description of the Background
In the field of medical technology, there is frequently a necessity to administer drugs locally. To provide an efficacious concentration to the treatment site, systemic administration of medication often produces adverse or toxic side effect for the patient. Local delivery is a preferred method in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Thus, local delivery produces fewer side effects and achieves more effective results.
The drug-eluting stent also provides for the local administration of a therapeutic substance at the diseased site. In order to provide an efficacious concentration to the treated site, systemic administration of such medication often produces adverse or toxic side effects for the patient. Local delivery is a preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. As such, local delivery thus produces fewer side effects and achieves more favorable results.
Peripheral artery disease affecting the lower extremities is common in an aging population, affecting 10-14% of men over the age of 65, and 20% of men and women reaching the age of 75. The progression of lower extremity arterial disease can lead to loss of mobility, limb pain, gangrene and amputation, as well as increased mortality. Mortality rates at five years in patients with Peripheral Vascular Disease (PVD) are approximately 30%; these rates reach 44% in patients with severe peripheral artery disease. The superficial femoral artery (SFA) is the most commonly diseased blood vessel in the peripheral (lower limb) vasculature, due to its characteristics: a long vessel surrounded by flexion points, with few collateral vessels. These characteristics promote more diffuse disease, and slow flow and flow dynamics.
Prevention of restenosis after endovascular treatment in the peripheral arteries is a major challenge for the interventionalist, particularly in the superficial femoral artery (SFA), in which long, heavily calcified, and/or chronically occluded lesions are often present. Self-expanding stents, with their elastic properties, have been shown to be of benefit in the revascularization of the SFA. Stent implantation, by providing a permanent scaffold for the vessel, reduces vessel recoil and remodeling, two of the contributing factors in restenosis. However, neointimal hyperplasia, the major mechanism of restenosis, remains a significant problem in the peripheral arteries.
Accordingly, to reduce the partial or total occlusion of the artery by the collapse of arterial lining, and to reduce the chance of the development of thrombosis and restenosis, an expandable, intraluminal prosthesis coated with a therapeutic or beneficial agent, one example of which includes a drug-eluting stent, is implanted in the lumen to maintain the vascular patency.
One method of medicating a stent is with the use of a polymer coating incorporating a drug. To fabricate the polymer coating, a suitable polymer is usually dissolved in a solvent or blend of solvents, followed by applying the solution onto the stent, for example, by spraying or dipping. To complete the process of fabricating the stent coating, the stent is dried and/or baked to remove the solvent.
Examples of solvents currently used to dissolve biocompatible polymers for fabricating stent coatings include dimethylacetamide (DMAC), dimethylsulfoxide (DMSO), dimethylformamide (DMF), and formamide. These solvents or similar solvents with relatively high boiling points, for example, above 120° C. at ambient pressure, and/or low volatility, for example, having vapor pressure under 15 Ton at room temperature, have a tendency to evaporate very slowly. Prolonged period of time may be needed to allow the solvent to fully evaporate from the coating because residual or trace amounts of the solvent may remain in the coating composition, which may produce an adverse response subsequent to the stent implantation. Baking of the stent at relatively high temperatures may be needed to facilitate the process of the solvent removal. The baking temperatures used for this purpose, should not exceed the temperature at which the drug can be adversely affected, however. The embodiments of the present invention provide methods for facilitating the evaporation of the solvent from the coating composition.
Therefore, a need exists for a drug eluting implantable medical device, with a low residual solvent content, that via local application of therapeutic agents provides for an effective pharmacokinetic (PK) profile of drug tissue concentration over time and successfully inhibits or reduces restenosis in peripheral arteries.